Devices and methods for drug administration and mixing, and training of proper techniques therefor

ABSTRACT

A device for training users in a proper mixing of pharmaceutical components, or for aiding in the mixing, or for performing the mixing, and administration of pharmaceutical components is disclosed. The device comprises a housing for receiving a pharmaceutical delivery device containing the pharmaceutical components. There is also a microcontroller disposed in the housing and a motion/orientation detection device disposed within or on the housing and in communication with the microcontroller. A method for use of the device is also disclosed, along with a substance for use as one of the pharmaceutical components.

BACKGROUND

Pharmaceutical products intended for delivery by injection may be storedin vials or pre-filled syringes. In either case, when such productsconsist of two or more liquid and/or solid phases, they must be agitatedprior to administration for optimum result, usually by manual shaking.Health Care Professionals (HCPs) and in some cases patients orcaregivers, may not provide consistent agitation for a number ofreasons. They may not be familiar with the pharmaceutical product; theymay have habituated experience of similar pharmaceutical products whichthey presume to have the same or similar preparation steps; or they maymis-time the shake duration or required shaking vigor, mistakenlyunderestimating the time or vigor required to properly agitate thedevice and adequately mix the product.

SUMMARY OF THE DISCLOSURE

It is an aim of the present disclosure to provide a device that wouldprovide the HCP with the knowledge and experience of the minimumduration and vigor of shaking required for the preparation of variouspharmaceutical products such as, for example, INVEGA TRINZA™, whichconsists of particles in a suspension. It is also an aim to provideanother device that alerts the user, for example when too much time hasexpired after mixing and the mixing step must be repeated. It is also anaim to disclose yet another device only works with the specified syringefor a particular product, and not, for example, a competitor syringe.This ensures that people do not mistakenly use the device with the wrongdrug product, and can also be used as a means for differentiating oneproduct relative to a competitor.

Accordingly, various embodiments of devices and methods to operate suchdevices to fulfill the needs and/or mitigate the shortcomings aredisclosed. The present invention is defined by the appendant claims.

For example, in one aspect of the invention, a device is provided fortraining users how to properly mix pharmaceutical components. In anotheraspect, a device is provided for mixing pharmaceutical components, andassisting with the administration of properly inked pharmaceuticalcomponents. In another aspect, a device for mixing and administratingproperly, mixed pharmaceutical components is disclosed. In anotheraspect, a device for attachment to a pharmaceutical delivery device andfor assisting with the administration of properly mixed pharmaceuticalcomponents is disclosed. All of these devices are referenced herein (inboth the description and claims) as the “device”. The device may includea housing, for example a housing which extends along a longitudinalaxis, for example with a power source disposed in the housing. Amicrocontroller may also be disposed in the housing and electricallypowered by the power source as well as a user notification device and amotion or orientation detection device (“motion/orientation detectiondevice), e.g. an accelerometer, disposed in the housing and electricallyconnected to the microcontroller. In this device, the microcontroller isconfigured to detect a motion and/or orientation of the housing andindicate via the user notification device as to whether the motionand/or orientation of the housing (e.g. when being shaken) during one ofa drug administration or a training event is sufficient with respect topredetermined thresholds including magnitude of the force applied duringshaking, acceleration of the housing during shaking, the orientation ofthe housing and/or duration of shaking.

Another aspect of the invention includes a method of operating such adevice. The method can be achieved by determining from themotion/orientation detection device, e.g. accelerometer, if themagnitude of the motion and/or orientation of the housing are sufficientwith respect to predetermined thresholds including magnitude of theforce applied during the shaking, acceleration, the orientation of thehousing and duration of such shaking; and announcing via the usernotification device as to whether the motion or orientation of thehousing being shaken during one of a drug administration or a trainingevent meets the predetermined thresholds.

In addition to the various aspects described above, other featuresrecited below can be utilized in conjunction therewith to arrive atdifferent permutations of the invention. For example, the device mayinclude a start switch electrically connected to the microcontroller;the accelerometer may include a 3-axis accelerometer; the accelerometeris configured to activate the microcontroller upon detection ofmovements of the housing during one of a drug administration or atraining event; the microcontroller is configured to detect when shakingof the housing has ended prematurely, or if the level of shaking vigorhas reduced to a level below the pre-set threshold, to enter a pausemode to allow the user to restart the shaking during one of a drugadministration or a training event; the microcontroller is configured toset a timer and determine when a maximum allowable time after shaking ofthe housing has elapsed to warn the user to shake the device againduring one of a drug administration or a training event; the housing mayinclude a syringe barrel element with finger flange and one end and abarrel tip spaced apart along the longitudinal axis; the housing mayinclude a body with a slot sized to accept a syringe barrel; the housingmay include a housing provided with a compartment and a lid to receivean entire syringe; the housing may include an elongated bodyapproximately the same length as a syringe barrel such that a syringe isinserted into a syringe receiving hole in the body and retained by thecompressive force applied by the finger-like members between a syringefinger flange and a body base; the housing may include a body with asyringe accepting slot sized to accept a syringe barrel; the housing mayinclude a puck-like body with a syringe accepting hole so that in use asyringe is inserted into the syringe accepting hole and is held in placewith a user's thumb on an underside thumb grip.

These and other embodiments, features and advantages will be understoodby those skilled in the art when taken with reference to the followingmore detailed description of the exemplary embodiments of the inventionin conjunction with the accompanying drawings that are first brieflydescribed.

BRIEF DESCRIPTION OF THE FIGURES

The foregoing and other features and advantages of the invention will beunderstood from the following, more particular description of preferredembodiments of the invention, as illustrated in the accompanyingdrawings.

FIG. 1A is a block diagram schematic of the electronic system/device ofthe present disclosure;

FIG. 1B illustrates a standalone mimic trainer embodiment, general view;

FIG. 2 illustrates a standalone mimic trainer embodiment, orthographicviews;

FIG. 3 illustrates a syringe barrel attachment embodiment, showingdevice separate from, and attached to syringe;

FIG. 4 illustrates a syringe barrel attachment embodiment, front, leftand right side;

FIG. 5 illustrates a syringe barrel attachment embodiment, front, topand bottom side;

FIG. 6 illustrates a syringe case embodiment, general view showingsyringe next to open case;

FIG. 7 illustrates a syringe case embodiment, general view showingsyringe inside open case;

FIG. 8 illustrates a syringe case embodiment, general view showingclosed case;

FIG. 9 illustrates a syringe case embodiment, general view showingfront, top and side view;

FIG. 10 illustrates a syringe pot embodiment with syringe inside,showing front and side views;

FIG. 11 illustrates a syringe pot embodiment without syringe showingfront and side views;

FIG. 12 illustrates a syringe finger rest attach embodiment, withoutsyringe;

FIG. 13 illustrates a syringe with and without syringe finger restattach embodiment, with—side view;

FIG. 14 illustrates a syringe with and without syringe finger restattach embodiment, with—front view;

FIG. 15 illustrates a syringe puck embodiment, with syringe;

FIG. 16 illustrates a syringe puck embodiment, without syringe

FIG. 17 illustrates a trainer evoke embodiment;

FIG. 18 illustrates a packaging attachment embodiment A, attached tosyringe while in tray;

FIG. 19 illustrates a packaging attachment embodiment A, detached fromsyringe;

FIG. 20 illustrates a packaging attachment embodiment B, attached tosyringe tray;

FIG. 21 illustrates a packaging attachment embodiment B, detached fromsyringe tray;

FIG. 22 is a chart illustrating the threshold requirement for a devicecontaining sediment;

FIG. 23 is a chart illustrating how a proportion of users will fail toprovide sufficient vigor to adequately mix the product un-aided;

FIG. 24 is a chart illustrating the role of a device or aid, to modifyuser behavior so all shake with sufficient vigor to exceed the requirethreshold;

FIG. 25 illustrates a syringe case embodiment with LCDdisplay—sedimentation mixing represented using display;

FIG. 26 illustrates LCD screen conditions showing stages of mix fromsediment on left to mix on the tight;

FIG. 27 is a diagram of a mixing and administration method forpharmaceutical components or drug according to the present disclosure;and

FIG. 28 is diagram showing a method of operation of the implementedsystem/device of the present disclosure.

The accompanying drawings, which are incorporated herein and constitutepart of this specification, illustrate presently preferred embodimentsof the invention, and, together with the general description given aboveand the detailed description given below, serve to explain features ofthe invention (wherein like numerals represent like elements).

LIST OF REFERENCES

The following is a list of reference numerals relied upon in thefigures:

-   -   100 Mimic trainer embodiment, plunger replacement    -   101 Finger flange    -   102 Light emitting feedback window    -   103 Barrel    -   104 Barrel tip    -   105 Syringe plunger rod    -   106 Syringe back stop    -   107 Syringe Barrel    -   108 Rubber stopper    -   109 Barrel attach embodiment body    -   110 Light emitting feedback window    -   111 Syringe clamping slot    -   112 Syringe retaining spring clip    -   113 Case lid    -   114 Case body    -   115 Case liner    -   116 Case hinge    -   117 Syringe    -   118 Springe clip    -   119 Light emitting panel    -   120 Lid catch    -   121 Elongated body    -   122 Light emitting band.    -   123 Syringe receiving hole    -   124 Base of body    -   125 Syringe accepting slot    -   126 Light panel    -   127 Body    -   128 Syringe accepting hole    -   129 Light emitting band.    -   130 Thumb grip    -   131 Finger grip    -   132 Thumb grip    -   133 Light emitting window    -   134 Body    -   135 Body    -   136 Blister tray packaging    -   137 Syringe    -   138 Side interference clips    -   139 Syringe slot    -   140 Light emitting band    -   141 Device attached to blister tray    -   142 Blister tray    -   143 Blister tray film    -   144 Syringe    -   145 Return clips    -   146 Light emitting strip    -   147 Device Body    -   148 Case base    -   149 Case top    -   150 3 Axis Accelerometer    -   151 Battery    -   152 Battery latch    -   153 Start switch    -   154 Microcontroller    -   155 User notification    -   200 Device    -   202 Housing    -   301 LCD    -   302 First state    -   303 Second state    -   304 Third state    -   305 Final state    -   401 Step: User applies shaking motion    -   402 Step: Detect motion and/or orientation    -   403 Step: Compare magnitude of motion and/or orientation with        one or more thresholds    -   404 Step: Does motion and/or orientation meet the threshold(s)?        Yes/No    -   405 Step: Notify user that motion and/or orientation meets the        threshold(s)    -   406 Step: Notify user that motion and/or orientation does not        meet the threshold(s)

DETAILED DISCLOSURE

The following detailed disclosure should be read with reference to thedrawings, in which like elements in different drawings are identicallynumbered. The drawings, which are not necessarily to scale, depictselected embodiments and are not intended to limit the scope of theinvention. This detailed disclosure illustrates by way of example, notby way of limitation, the principles of the invention. This disclosureclearly enables one skilled in the art to make and use the invention,and describes several embodiments, adaptations, variations, alternativesand uses of the invention, including what is presently believed to bethe best mode of carrying out the invention.

As used herein, the terms “about”, “approximately”, or “substantially”for any numerical values or ranges indicate a suitable dimensionaltolerance that allows the part or collection of components to functionfor its intended purpose as described herein. More specifically,“about”, “approximately”, or “substantially” may refer to the range ofvalues ±10% of the recited value, e.g. “about 90%” may refer to therange of values from 81% to 99%. In addition, as used herein, the terms“patient,” “host,” “user,” and “subject” refer to any human or animalsubject and are not intended to limit the systems or methods to human,animal or medical use, although use of the subject invention in a humanpatient represents a preferred embodiment. Reference to “g” in terms ofacceleration means 9.81 ms⁻², approximately 10 ms⁻².

The exemplary embodiments shown and described here may utilize anelectronic system such as an electronic circuit mounted on a printedcircuit board (PCB), which may include means to supply and controlelectrical power, means to measure spatial acceleration, means to timethe duration of shaking and means to communicate the device state to theuser as shown in FIG. 1A.

FIG. 1A shows components of a device 200 for training or aiding users ina proper mixing of pharmaceutical components. The device includes ahousing 202, a microcontroller 154 disposed in or on the housing 202 andan accelerometer 150 disposed in or on the housing 202 and electricallyconnected to the microcontroller 154 so that the microcontroller 154 isconfigured to detect a motion and/or orientation of the housing 202. Themicrocontroller 154 may be disposed in the housing 202, such that it iscontained by the housing 202. Alternatively the microcontroller 154 maybe disposed on the housing 202 such that it is attached to the housing202. Similarly the accelerometer 150 may be disposed in the housing 202such that it is contained by the housing 202, or alternatively theaccelerometer 150 may be disposed on the housing 202. Motion of thehousing 202 may include shaking of the housing 202 by a user. Shakingmay include reciprocating motion of the housing 202 for example in an upand down direction, or in a side to side reciprocating motion, or acombination of both, relative to the ground. Orientation of the housing202 may be measured with reference to an approximately 1 g accelerationin the direction of gravity. The orientation may also be determinedbased on the integration of acceleration forces experienced by theaccelerometer 150 with respect to time.

Referring still to the embodiment of FIG. 1A, the device 200 comprises apower source 151 disposed in the housing 202 and electrically connectedto the microcontroller 154. The power source 151 may be disposed orcontained in the housing 202 and may for example comprise a battery 151or any other suitable power source, such as a capacitor. The powersource 151 may be connected to the microcontroller 154 in order to powerthe microcontroller 154. It will be appreciated that various types ofpower source may be provided.

Specifically, the microcontroller 154 may be powered by the power source151. The microcontroller 154 may optionally be powered by the powersource 151, e.g. battery. This may be useful whilst the device 200 is intransit or if the device 200 is not to be used for a prolonged period oftime.

The microcontroller 154 may be configured to detect low remaining poweravailability of the power source 151. In this case the microcontroller154 can detect when the power source 151 is insufficient to achieve allthe functions of the device 200, or if the power source 151 will beinsufficient in the near future, e.g. to power the microcontroller 154or accelerometer 150 such that they can function as intended or in theusual manner. This can be done by monitoring the voltage supplied by thepower source 151, how the voltage varies under different loads, whatpower is available, or how stable the supply is. If a rechargeablebattery is used, then the microcontroller 154 may additionally be ableto monitor the health of the battery.

Still referring to the embodiment of FIG. 1A, the microcontroller 154may be configured to detect an error or fault in the functioning of thedevice 200. For example, the fault may be in one or more of themotion/orientation device 150, the housing 202 or its attachment to orcontainment of a pharmaceutical delivery device. As an example, in thecase of an accelerometer 150 or any other motion/orientation device, themicrocontroller 154 may receive an unexpected signal, or it may receiveno signal at all. If this is detected by the microcontroller 154, theunexpected signal or lack of signal may be detected as an error in thedevice 200. Similarly, the microcontroller 154 may be able to detect thestate of the housing 202 or of a contained pharmaceutical deliverydevice, e.g. whether the housing 202 is closed and/or the deliverydevice is properly or sufficiently inserted into the housing 202.Similarly the microcontroller 154 may be able to detect an unexpectedsignal or no signal, e.g. from the microcontroller 154 or accelerometer150, when there should be and register this as an error or fault.

In a device 200, as described above, in which the microcontroller 154detects a low remaining power availability of the power source 151 orwhen the microcontroller 154 detects the fault or error, it may performone or more of: issuing an alert representative of the low remainingpower availability to the user (for example via the user notificationdevice 155), and/or preventing activation of the pharmaceutical deliverydevice for delivery of the pharmaceutical components to a user. Thedevice 200 may issue an alert to the user that there is a low poweravailability. This allows the user to take rectifying action, or to knowthat the device 200 may not be usable now or in the future. If the powerdrops to a certain point it is possible that the circuit, themicrocontroller 154, or any other components may become unreliable. Forexample, an unstable power supply to a microcontroller 154 could lead tounexpected results from the microcontroller 154. If this is the case,then it is possible that the device 200 could encourage incorrectbehavior of the user, such as not requiring the completion of a shakingevent or not correctly detecting a threshold. This could lead to use ofpharmaceutical components which are not properly mixed. In this case,the microcontroller 154 may prevent activation of the pharmaceuticaldelivery device for the delivery of pharmaceutical components to a user.Prevention of activation of the delivery device may be achieved in anumber of ways. Wherein the shaking device 200 is also the drug deliverydevice, the microcontroller 154 may be connected to an activatable lockwhich acts against the delivery device deliver mechanism or activator toprevent expulsion of the pharmaceutical components, e.g. via a stopwhich can be moved into a locked position from an unlocked position andvice-a-versa. The lock may be a device which obstructs the flow of thepharmaceutical components out of the device through a nozzle, such as avalve. Alternatively, in the case where the drug delivery devicecomprises an actuator for actuating the delivery of the pharmaceuticalcomponents, the lock may be a component which obstructs the actuatorfrom expelling the components. In the case where an actuator is drivenautomatically by a spring, the lock may also be a component whichdisengages the spring from the actuator, such that it cannot expel thecomponents from the drug delivery device. In the case where the shakerdevice of the present invention engages with a separate drug deliverydevice, such as clipping on or containing the device, then the shakerdevice may prevent activation of the drug delivery device by othermeans. In one example, the drug delivery device comprises a circuitwhich may communicate with the microcontroller 154 of the shaker device.Communication may be achieved by electrical connection when the twodevices are connected, or alternatively by wireless communication. Thecircuit of the drug delivery device may be active or it may be passive,it may also comprise its own power source, or share the power source 151of the shaker device. In this aspect the drug delivery device mayachieve prevention of activation of the pharmaceutical delivery deviceby the same means as described above. Alternatively, the shaker devicemay comprise an actuatable lock which interacts with a correspondinglock on the drug delivery device. The actuatable lock of the shakerdevice 200 may mechanically couple with a corresponding lock on the drugdelivery device to prevent actuation of the drug delivery device.Alternatively, the actuatable lock of the shaker device 200 may be amoveable magnet. When the drug delivery device is engaged with theshaker device 200 the moveable magnet may be moveable between a firstposition, in which the delivery device may not be activated, and asecond position in which the delivery device may be activated. Forexample, in order to prevent activation of the delivery device, themoveable magnet may be moved such that a magnetic ball in the deliverydevice obstructs the expulsion of the pharmaceutical components.Alternatively, to a moveable magnet, the shaker device 200 may comprisean electromagnet which may be activated or deactivated to provide amoving magnetic field which may selectively prevent activation of thedelivery device. 100491 The device 200 may comprise a delivery deviceidentification unit in communication with the microcontroller 154. Inthis case the device 200 may have means of identifying delivery devices.The device 200 may be capable of reading an RFID tag, a barcode, or texton the delivery device. In this case the device 200 may be capable ofdetecting if the correct delivery device is being used. The deliverydevice identification unit may be configured to read data on datastorage means of a delivery device contained in use in the housing 202,wherein the read data is characteristic of the pharmaceutical componentscontained in the device 200 and/or delivery device itself. In this case,the microcontroller 154 may identify the pharmaceutical components inthe delivery device. The data may comprise one of more of: an expirationdate of the pharmaceutical components, whereby, the microcontroller 154is configured to alert a user via a user notification device 155 of thedevice 200 if the current date as determined by the microcontroller 154exceeds the expiration date, and/or data identifying the pharmaceuticalcomponents contained within the delivery device, for example dataindicative of manufacturer or composition of the pharmaceuticalcomponents, whereby the microcontroller 154 is configured to alert auser via a user notification device 155 of the device 200 if the dataidentifying the pharmaceutical components does not match or sufficientlycorrespond to permitted pharmaceutical components as stored in themicrocontroller 154 or in memory connected thereto. The microcontroller154 may include a clock which keeps track of the current date and/ortime, or the microcontroller 154 may be configured to receive thecurrent date and/or time from an external source, such as a radiosignal. In either case the current date may be compared with anexpiration date of the pharmaceutical components. The data read from thestorage means may include the specific expiration date, or informationwhich allows the expiration date to be calculated. For example, the dataread from the storage may include a production date and an indication ofhow long the pharmaceutical components may be stored. The data mayinclude data identifying the components themselves. This data may be aname of a component which may or may not be encoded. The encoded name ofthe components may then be correlated to the actual components. The dataidentifying the pharmaceutical components may also be used to identifythe correct level of vigor and/or time for shaking for mixing thecomponents prior to shaking. The user notification device 155 mayindicate to the user instructions for properly mixing the pharmaceuticalcomponents. The microcontroller 154 may further alert the user if thedata identifying the components does not match or sufficientlycorrespond to permitted pharmaceutical components. Advantageously thisalerts the user in cases where the incorrect pharmaceutical componentsare about to be used. The correct components to use may be stored in themicrocontroller 154 or memory prior to the use of the device 200.

The above-mentioned data may comprise one or more of: the expirationdate of the pharmaceutical components, whereby the microcontroller 154is configured to prevent activation of the pharmaceutical deliverydevice for delivery of the pharmaceutical components to a user if thecurrent date as determined by the microcontroller 154 exceeds theexpiration date, and/or data identifying the pharmaceutical componentscontained within the delivery device, for example data indicative ofmanufacturer or composition of the pharmaceutical components, wherebythe microcontroller 154 is configured to prevent activation of thepharmaceutical delivery device for delivery of the pharmaceuticalcomponents to a user if the data identifying the pharmaceuticalcomponents does not match or sufficiently correspond to permittedpharmaceutical components as stored in the microcontroller 154 or inmemory connected thereto. In these examples, the microcontroller 154 iscapable of preventing use of the delivery device in the cases where thepharmaceutical components have expired or are not those intended foruse. This may be achieved via the mechanism described above.

As shown in FIG. 1B, which shows one specific embodiment of thisdisclosure, the housing 202 may extend along a longitudinal axis L-L.The housing 202 may be elongated such that it mimics or is a suitableshape for supporting a container for pharmaceutical components.

The housing 202 comprises a major longitudinal axis L-L. Drug deliverydevices may be elongated or have a major longitudinal axis, as forexample shown in FIG. 1B. Such a device 200 may also be elongated orhave a major longitudinal axis. This may be to mimic or contain a drugdelivery device or other container for pharmaceutical components, forexample a vial.

The housing 202 may be adapted to receive a drug delivery device havinga major longitudinal axis, and to further align its major longitudinalaxis along the major longitudinal axis of the drug delivery device, asfor example shown in FIG. 3. Advantageously, such a device 200 may allowthe drug delivery device to be received in a particular orientation.Since the axes of the device 200 and of the drug delivery device arealigned, the alignment of the drug delivery device with respect to anyother components which may be fixed to the housing 202 is known. If, forexample, the orientation of the microcontroller 154 is known withrespect to the housing 202, and the major longitudinal axes of the twodevices are aligned, then the orientation of the microcontroller 154with respect to the drug delivery device is known.

The microcontroller 154 may be configured to detect a motion and/ororientation of the housing 202 with respect to motion along or about thelongitudinal axis, in which case the accelerometer 150 is able todistinguish between acceleration forces along the longitudinal axis ofthe housing 202 and acceleration forces about the longitudinal axis. Anaxis of an accelerometer 150 may be aligned with the longitudinal axisof the housing 202 such that measurements by that axis correspond tomotion along the longitudinal axis of the housing 202. Alternatively theaccelerometer 150 may have at least two axes which are not aligned withthe longitudinal axis of the housing 202 and the forces may be resolvedin order to determine the motion along the longitudinal axis. Theaccelerometer 150 may also detect motion in any other direction, orrotation about any other axis. The accelerometer 150 may also detect theorientation of the housing 202 with respect to the motion which is beingapplied to it. The method of operation of the device 200 as controlledby the microcontroller 154, e.g. via executable instructions executingtherein, is shown in FIG. 28.

With reference now to FIG. 28, in a shaking event a user applies 401 ashaking motion to the device. The device detects 402 the motion and/orthe orientation of the device. The device compares 403 the magnitude ofthe motion and/or the orientation of the device with respect to one ormore thresholds. At 404 if the motion and/or orientation of the devicemeets the threshold or thresholds then the process moves to notify 405the user that the motion and/or orientation meets the threshold orthresholds. At 404, if the motion and/or orientation of the device doesnot meet the threshold or thresholds then the process moves to notify406 the user that the motion and/or orientation does not meet thethreshold or thresholds.

As shown in FIG. 1A the device 200 may include a user notificationdevice 155 in communication with the microcontroller 154. The usernotification device 155 may provide user notifications as instructed bythe microcontroller 154. The user notification device 155 may compriseone or more of: a display, a tactile feedback unit, a light emittingdevice and/or a vibratory alert unit. The user notifications may includeone or many of a notification that the device 200 is on, the device 200is off, shaking has commenced, shaking has paused, shaking has stopped,the wrong frequency of shaking is being applied, the correct frequencyis being applied, sufficient shaking has taken place, or too much timehas elapsed post completed shaking. The user notification device 155 mayindicate notifications to the user by visual means such as a lightemitting component or an LCD screen. For example an LCD displaycomprising a number of pixels or other elements may be used. The displaymay be of a type which reflects light, a type which transmits abacklight, or a type which emits light. A light emitting device mayinclude a light emitting diode. The light emitting diode may beconfigured to emit light of one particular colour, or of a number ofcolours. The light emitting device may also comprise a light bulb.Optionally the user notification device 155 may indicate to the user byaudible means, such as a buzzer or a speaker. Optionally the usernotification device 155 may be tactile by means of vibration or thephysical movement of a component by motor. Beneficially, the userfeedback allows the user to modify his or her behavior in response tofeedback from the device 200. In one example, in use, if the user beginsshaking the device 200 at a suitable level of vigor but then ceases tosustain the sufficient level of vigor as measured by the accelerometer150, the device will notify the user to apply more vigor. This could beby an audible alarm, a visual cue or by tactile vibration. Alternativelythe device 200 can provide a positive feedback whilst attaining asufficient level of vigor and then removing the feedback when the userdrops below this. For example, tactile feedback can confire that theshaking is sufficient which will cease when the user no longer attainsthis level. Alternatively a light may be on when the user is shakingsufficiently and may turn off when the level of shaking is insufficient.The user notification device 155 may be mounted on an external surfaceof the housing 202 for notifying the user as to its status. This may beparticularly useful in the case of user notification devices providingvisual feedback since this places them in a position where they be moreeasily seen by the user. Although any user notification device maybenefit from being positioned in this manner, in closer proximity to theuser.

In the case of the user notification device 155 being a display, themicrocontroller 154 may be configured to indicate via the display astate of mixing or simulated mixing of the pharmaceutical components ina real-time manner. In this way the user is provided with feedback whichallows the user to understand how far through the shaking event theyhave progressed. This may be an indication of how much time the user hasbeen shaking under satisfactory conditions. This may also be anindication of how well the components have or would have been mixed. Forexample, shaking at a higher intensity may promote mixing of thecomponents, in which case the display may be configured to indicate thatthe mixing has progressed further after the same duration of shaking ata lower intensity. As a further indication the microcontroller 154 maybe configured to change progressively the colour and/or pattern of oneor more display elements on the display as shaking takes place untilsufficient shaking has taken place for satisfactory mixing orsatisfactory simulated mixing of the pharmaceutical components fordelivery. This allows the user to be made aware of the progression ofthe shaking event or of the mixing of the pharmaceutical components bymeans of changing the colour of one or more display elements. Forexample a display element may change from red to green, from green tored, or indeed any other change in colour, to indicate that the mixinghas progressed. The display may also change the pattern of the displayelements. For example this could be a bar graph which progresses, or itmay be an arrangement of display elements which indicate a more sparsearrangement as the mixing progresses. The display may also use anycombination of these changes in the display elements to indicate to auser that satisfactory mixing or satisfactory simulated mixing isoccurring.

Furthermore, in the case where the device 200 includes a display 301,and with reference to FIG. 26, the microcontroller 154 may be configuredto display at least two types of display elements on the display 301which are grouped together in at least two discrete portions of thedisplay 301 prior to commencement of shaking, and which progressivelymix with each other on the display 301 so long as shaking continues at asufficient enough or pre-defined force and/or for a sufficient enough orpredefined duration, until such time that it is determined thatsufficient shaking has taken place for satisfactory mixing orsatisfactory simulated mixing of the pharmaceutical components fordelivery, at which time the at least two types of display elements arewholly integrated with each other in a regular pattern across thedisplay 301. In this way the user is provided with an intuitive displayof the progress of the mixing. In a training event there may be nopharmaceutical components for the user to see. In this case the display301 provides a visual feedback capable of representing how well mixedthe components are. In the case of either a training event where thepharmaceutical components are present or an actual mixing event, theuser may not be able to see the pharmaceutical components in situ or itmay be difficult to see the degree of mixing due to the visualproperties of the pharmaceutical components. In any case, the display301 provides feedback to the user which can be easily identified ascomponents mixing. There may also be more than two types of displayelement which may achieve a similar effect as the two types of displayelement.

In a device 200 in which there are only two types of pharmaceuticalcomponent to be mixed or simulated for mixing, and wherein there areonly two types of display element, one of the types of display elementmay correspond to one of the pharmaceutical components and the othertype of display element may correspond to the other one of types ofdisplay element. Corresponding display elements with pharmaceuticalcomponents in this way provides an intuitive display which represents astate of mixing to the user or a progression of the mixing event. Thismay be extended to other compositions which include more than twocomponents wherein each component corresponds to a different type ofdisplay element. Further to this, two types of display element may beused to represent more than two pharmaceutical components.Alternatively, more than two types of display element may be used torepresent two pharmaceutical components.

The microcontroller 154 may be configured to detect in a shaking eventwhether the motion and/or the orientation of the housing 202 beingshaken during one of a pharmaceutical administration or a training eventis sufficient with respect to one or more predetermined thresholdsincluding one or more of: magnitude of the force applied to the device200 during the shaking, orientation of the housing 202, acceleration ofthe device 200, and duration of such shaking. A number of factors mayaffect the efficacy of the shaking in achieving mixing of pharmaceuticalcomponents. For example, a user who shakes the device 200 “harder” maybe causing a greater acceleration of the device 200 at either end of theswinging motion. This greater acceleration and harder shaking may causefaster mixing of the components as the forces which they experience willbe greater, causing better dispersion. Although “harder” shaking maylead to better mixing, it is also possible that for a particularcomposition of pharmaceuticals the added benefit of “harder” shakingabove a certain threshold may be diminishing. Hence, the device 200 mayonly require a certain threshold to be met and then record the shakingactivity from that threshold. In some cases the orientation of thehousing 202 may affect the mixing of the pharmaceutical components, inwhich case the device 200 will detect by the accelerometer 150 whichdirection the swinging action of the shaking is being applied in andprovide feedback accordingly. For example, the user may be shaking thedevice 200 across the longitudinal axis instead of along it. In thiscase the device 200 may ignore this shaking motion since it does notbenefit the mixing of the pharmaceuticals. Alternatively, it may beknown that shaking across the longitudinal axis may still benefit mixingof the pharmaceuticals and the device 200 can then include this shakingin the monitoring of the shaking activity. Shaking of the device 200across the longitudinal axis may contribute to the recording of theshaking activity to any of a lesser, the same, or even a greater degreethan shaking along the longitudinal axis. In a further aspect, if thedevice 200 includes a user notification device 155, the microcontroller154 may indicate to the user whether the motion or orientation of thehousing 202 being shaken is sufficient with respect to one or more ofthe predetermined thresholds.

Applicable sufficient thresholds for mixing two pharmaceuticalcomponents may be in one of the following ranges: 2 g to 15 g, 5 g to 12g, and 7 g to 10 g or at a threshold of 3 g, 4 g, 5 g, 6 g, 7 g, 8 g, 9g or 9.3 g. Suitable orientation of motion along the longitudinal axisfor mixing whilst may be substantially along the longitudinal axis, orvertically with respect to the ground, or in the range +/−2 degrees eachside of the longitudinal axis, +/−2 degrees each side of thelongitudinal axis, +/− 10 degrees each side of the longitudinal axis,+/−20 degrees each side of the longitudinal axis, +/−30 degrees eachside of the longitudinal axis. These thresholds may be suitable formixing the components of INVEGA TRINZA™ as described in further detailbelow.

Referring again to FIG. 1A, the device 200 comprises a start device 153in communication with the microcontroller 154. The start device 153 maybe configured to continence detection for the shaking event by themicrocontroller 154. Advantageously the start device 153 provides aninput to the device 200 to indicate with precision when the device 200is going to be used. This may allow the device 200 to conserve powersince it may enter a low power mode, in which the microcontroller 154and/or other components of the device 200 are configured to draw lesspower from a power source 151. The start device 153 may be one of astart switch in communication with the microcontroller 154, a startbutton in a user interface displayed by a touch sensitive display screenof the device, or the start device 153 may be a motion sensitive devicewhich may indicate that detection of the shaking event should commencewhen the housing 202 is moved. The use of a start device 153 allows theuser to choose when the device 200 may be prepared to detect the shakingevent. This may be useful if, for example, the device 200 is to becarried around or shipped to another location and will help preserve thepower source 151 for actual use rather than accidental triggering of thedevice 200.

Wherein the start device 153 is a start switch, the start switch may beconfigured to activate the microcontroller 154 from a power conservationmode into an active mode upon detection of the movement of the housing202 during one of a drug mixing and administration event, or a trainingevent. This allows the device 200 to conserve power when it is not inuse or when it is not about to be used. The start switch 153 may beconfigured to activate the microcontroller 154 at one of a number ofthreshold levels of movement of the housing 202. For example, the startswitch 153 may be configured such that a user picking up the device 200activates the microcontroller 154. Alternatively the start switch 153may be configured such that a user is required to give the device 200 asharp impulse in order to activate the microcontroller 154.Alternatively the start switch 153 may be configured such that the usermust shake the device 200 more than once in order to activate themicrocontroller 154.

During such a power conservation mode the microcontroller 154 may beconfigured during the power conservation mode, to draw reduced powerwith respect to the active mode, or no power at all, from the powersource 151. In this way the device 200 may conserve power when it is notbeing used. This advantageously saves the use of a power source 151 forwhen it is needed. In a case where the power source 151 is a battery,the battery charge may be conserved during periods of inactivity toprolong the lifetime of the battery in the device 200. Other powersources may also benefit from the conservation of their use.

Alternatively or additionally to a start switch, the accelerometer 150may be configured to commence detection for the shaking event upondetection of movement of the housing 202 in excess of a predeterminedlevel during one of a pharmaceutical administration or a training event.Beneficially in this aspect the user may simply start shaking the device200 and the device 200 will begin recording the shaking automatically.Advantageously, such a device does not necessitate physical componentssuch as switches or a touch screen on the outside of the device 200.This may allow the device 200 to either be free from external physicalcomponents or reduce the number of external physical components on thedevice 200. This can improve the usability of the device 200 or make itsimpler to operate.

The microcontroller 154 may be configured to detect via theaccelerometer 150 when shaking of the housing 202 has ended prematurely.The microcontroller 154 receives a signal from the accelerometer 150 andmeasures how long the shaking has occurred for. If the shaking ceases,the microcontroller 154 receives a signal from the accelerometer 150which indicates that the shaking has stopped and the microcontroller 154can compare the actual duration of shaking to the required time ofshaking. The microcontroller 154 may also be configured to detect viathe accelerometer 150 if the level of shaking vigor has reduced to alevel below the one or more pre-set thresholds. Even if the user has notstopped shaking the device 200, the degree of shaking may not be enoughto meet the requirements for mixing of the pharmaceutical components. Inthis case the microcontroller 154 is configured to detect that the forceis not high enough to meet the threshold. The microcontroller 154 mayalso be configured to detect if the average level of shaking vigor overa predetermined time of the shaking event reduces to a level below oneor more pre-defined thresholds. In this aspect a greater degree offlexibility by the shaking measurement is achieved. More than onethreshold may be set in order to more accurately determine whether thecorrect degree of shaking has occurred. One threshold may be set thatrequires a lower intensity of shaking for a longer time, whilst anotherthreshold may be for a higher intensity over a shorter time period, orvice versa. This allows the device 200 to determine more accurately howwell the device 200 has been shaken. The microcontroller 154 may also beconfigured to detect via the accelerometer 150 if the component ofshaking in a predetermined direction is insufficient with respect to apredetermined level. Advantageously in such a device, themicrocontroller 154 is able to differentiate between shaking in a numberof directions, either along the longitudinal axis or in any otherdirection. The microcontroller 154 may also be able to determine if arotation in any direction is being applied to the device 200. Themicrocontroller 154 may give a certain weighting to the differentcomponents of the shaking action and/or may combine all of the readingsin the different directions to determine whether a total degree ofmixing has occurred.

The microcontroller 154 may be configured to notify a user ofunsatisfactory shaking when one or more of the events is detected.Notification to the user may be achieved by means of the usernotification device 155. This may be a positive feedback such as turn onor flashing a light such as an LED, a message displayed on a screen, avibration as tactile feedback, a sound emitted from a sound emittingdevice, or alternatively a negative feedback such as removing thepresence of any of these notifications.

The microcontroller 154 may be configured to notify a user ofsatisfactory shaking after or at a given time of passing of the shakingevent, such that satisfactory shaking is indicated by one or more of theevents not being detected. Notification may be given to the user byturning on or flashing an LED, changing the colour of an LED, displayinga message on a screen, giving tactile feedback such as vibration,emitting a sound from a speaker or a buzzer, or ceasing to provide anyof these notifications as positive feedback. Further to this, the giventime of passing may be at the completion of the shaking event such thatthe components are mixed or the simulated components are mixed.

The microcontroller 154 may be configured to enter a pause mode to pausedetection by the microcontroller 154 and subsequently allow the user torestart shaking and continue detection during the shaking event. A usermay need to stop shaking the device 200 momentarily so that their gripmay be adjusted for example, or in order to rest for a short while. Inany case the device 200 is configured so that a break in the shaking ofa sufficiently short time does not mean that the shaking cannot becontinued. If the user stops shaking to readjust his grip, he may thencontinue to shake the device 200 and the microcontroller 154 will exitthe pause mode and continue to measure the elapsed time and shaking.

The microcontroller 154 may be configured to start a timer and determinewhen a maximum allowable time after shaking of the housing 202 haselapsed to warn the user via the user notification device 155 to shakethe device 200 again during one of a drug administration or a trainingevent. Following a mixing procedure of a pharmaceutical composition thecomponents may begin to separate. After enough time has elapsed aftermixing, the composition will no longer be in a state in which the usershould be administering the composition any more, for example thesuspension of particles may have formed a sediment. Advantageously, whenusing a device 200 in which the microcontroller 154 determines themaximum allowable time, the user is notified when too much time haselapsed and the device 200 should be shaken again before administrationof the drug. In the case of a drug administration device or aid the userwill be notified and will need to shake the device again to mix thecomponents. In the case of a training event the user will be notified ofthe time after which the drug should have been administered and aids intraining.

As shown in the embodiment of FIG. 1A, the accelerometer 150 maycomprise a 3-axis accelerometer 150 which is configured to detect acomponent of shaking acceleration in each of three tangential directionsand provide data indicative of the components to the microcontroller154. Advantageously this device does not require the accelerometer 150to be positioned in a certain orientation in the device 200 to be ableto detect the longitudinal shaking of the device 200, or indeed anyother direction of shaking. Furthermore, the microcontroller 154 mayindicate to the user that shaking is not taking place in the correctdirection to mix the pharmaceutical components. Further to this, themicrocontroller 154 may also take into account shaking action in anumber of directions and use each of them to determine whether theshaking event has been successful.

With reference to the embodiments of FIGS. 1B and 2, the housing 202comprises syringe-shaped components located on or formed by the housing202. Advantageously, these components provide the components in atraining device which mimic those present in an actual syringe. In thisdevice the housing 202 provides tactile feedback to the user which issimilar to that which would be experienced from use of an actual syringeand assists in the ability to train a user.

Specifically the syringe-shaped components may comprise a syringe-likebarrel element 103 with finger flange 101 at one end and a barrel tip104 spaced apart along the longitudinal axis. These components aremimetic of key features of a syringe which the user may experiencehandling for the purposes of mixing pharmaceutical components.

The housing 202 may be configured to receive a pharmaceutical deliverydevice containing the pharmaceutical components. The pharmaceuticaldelivery device may be a syringe which the user may actuate manually bydepressing a plunger, or the delivery device may be an automaticinjector. In any case the housing has a form which allows the deliverydevice to be at least partially received. Further examples are given inthe rest of this disclosure.

With reference to FIG. 3, the housing 202 comprises a body 109dimensioned and/or shaped to accept a syringe barrel 107 or a vial. Thehousing 202 cooperates with the syringe barrel 107 or vial so that theuser is able to shake and mix the actual pharmaceutical componentswhilst still receiving the feedback from the device. Alternatively thedevice 200 may still be used to train the user in the proper techniquebefore applying it to the actual pharmaceutical components prior toadministration. When the device 200 is joined to the syringe barrel 107or vial, it is able to measure the shaking of the syringe barrel 107 orvial by proxy.

With reference to FIG. 6, the housing 202 comprises a compartment toreceive an entire syringe 117 or an entire vial. In this case the device200 may fully contain the syringe 117 or vial. This may aid users whofind the size or form of the syringe 117 or vial difficult to hold.Alternatively or additionally this device 200 may provide a degree ofprotection to the syringe 117. Fully receiving the syringe 117 or vialmay also disguise the syringe 117 or vial such that the contents may notbe easily viewed by people other than the user. In cases where there maybe a perceived social stigma in relation to syringes, this may benefitthe user.

Additionally the housing may comprise a moveable cover or lid 113 whichis moveable from a closed position, as shown in FIG. 7, completely orpartially over the compartment to an open position, as shown in FIG. 8,in which the syringe 117 or vial can be inserted into the compartment.Providing a lid 113 for the housing allows the user to selectivelyenclose the syringe 117 or vial in the housing such that it may beenclosed during transit or during a shaking event, and then opened whendrug delivery is intended.

Additionally the compartment may be dimensioned to receive the entiresyringe 117 or vial snugly and hold it securely within the housing. Inthis case the compartment fits the form of the syringe 117 or vial tosuch an extent that it is held securely in the housing. This may allowthe syringe 117 or vial to fit precisely in the housing such that theorientation of the syringe 117 or vial relative to the housing is known.

With reference to FIG. 10, the housing comprises art elongated body 121approximately the same length as a syringe barrel such that a syringecan be inserted into a syringe receiving hole 123 in the body 121 andretained by the compressive force applied by the finger-like membersbetween a syringe finger flange and a body base 124. In such a device,the body 121 of the housing may receive the syringe through a hole 123in the body. The syringe may be inserted until a stop position. At thestop position, the user may retain the syringe in the housing byretaining the finger flange towards a base 124 of the body. This may bedone by holding the finger flange between two fingers and the base ofthe body with a thumb.

The housing 202 may comprise an opening through which a discharge nozzleof a syringe or vial is extendable, or comprises an opening throughwhich at least a portion of the syringe barrel adjacent a syringe'sdischarge nozzle can extend. In this aspect only a portion of thesyringe or vial is contained in the housing 202. The syringe or vial maybe inserted into one end of the housing 202 which may provide a formwhich is easier for the user to grip.

Referring to the embodiments of FIGS. 4, 6, and 12, the housing 202comprises a body with a syringe accepting slot 125 sized to accept asyringe barrel or a vial containing the pharmaceutical components. Insuch a case the slot 125 may extend through the body of the device 200such that either end of the barrel of the syringe or the vial mayprotrude from either end of the slot 125. The slot may allow alongitudinal axis of the syringe or vial to be aligned with the device200 in a known relative orientation, thus allowing the orientation ofthe syringe barrel 107 or the vial to be known with respect to theground or with respect to the direction of shaking during a shakingevent.

Still referring to the embodiments of FIGS. 4, 6, and 12, the device mayfurther comprise a releasable clip 112, 118 in the slot configured toretain the syringe. The clip 112, 118 may be biased such that thesyringe barrel 107 may pass over it but a threshold force on the syringeis required to bias the clip 112, 118 again to remove the syringe. Thismay allow the device 200 to be kept with the syringe for storage. Thismay also aid the user in keeping the device 200 attached to the syringe117 securely during a shaking event. The releasable clip 112, 118 may bebiased by an elastic member such as a spring, or it may be biased by amoveable component such as a user operated switch or lever, allowing theuser to selectively lock the syringe in the slot of the device 200.

Referring now to FIG. 15 the housing 202 comprises a puck-like body 127with a syringe accepting hole 128 so that in use a syringe is insertedinto the syringe accepting hole and is held in place with a user's thumbon an underside thumb grip 130. In this aspect the user may hold thedevice in a grip with the thumb on the puck-like body 127. Some usersmay find this grip easier to maintain whilst shaking the device 200 in ashaking event.

With reference now to a syringe such as that shown in FIG. 3, thesyringe may comprise a discharge member adapted upon application offorce thereto to discharge the contents of the syringe. Such a dischargemember may be a bung contained within the body of the syringe andprovide a seal within the syringe to contain the pharmaceuticalcomponents. Applying pressure to the discharge member or the bungincreases the pressure of the pharmaceutical components causing them tobe discharged through an opening.

The device 200 may comprise an activator adapted to act upon thedischarge member of the syringe to expel its contents through thedischarge nozzle. Such an activator may be a plunger 105 which may bemanually pressed by a user in order to act upon the discharge member todischarge the pharmaceutical components. Alternatively the activator maybe a plunger which is acted upon by an automatic drive member such as aspring.

With reference to FIGS. 3 and 12 the housing 202 may further comprise anactivator opening through which the discharge member of the syringe canextend for application of force directly by the user from outside thehousing. In this aspect the housing may largely contain the syringe butthe syringe does not necessarily need to be removed from the housing forthe user to administer the pharmaceutical components. This may reducethe time that it takes a user to administer the pharmaceuticalcomponents following the successful completion of a mixing event.

The device 200 may be an attachment for a syringe wherein the housing202 is adapted to fit against a barrel of the syringe. In this aspectthe device may be attached to the syringe and sit against the barrel.Such a device may have a small size and may be simple to attach to asyringe.

Alternatively the device 200 may be an attachment for a syringe and thehousing 202 is adapted to fit around a barrel 107 of the syringe.Similarly this device 200 may have a small size and be simple to attachto a syringe, but may at least partially surround a syringe barrel 107to fit more snugly. The housing 202 may be adapted to fit around only aportion of the barrel 107 of the syringe, or the housing 202 may beadapted to fit around the whole of the barrel 107 of the syringe.

Alternatively the housing 202 may be formed of two hinged portions whichrotate in a hinged manner with respect to each other such that thehinged portions can close around the barrel and latch thereto. Thehinged portions may be connected by a rotatable hinge or by a livinghinge. At least one of the two portions may include a slot to receivethe barrel of the syringe. The two portions may be held together byapplication of a force by the user or they may be held together by amechanical latch, such as a latching member.

Alternatively to requiring a syringe which incorporates a dischargenozzle the housing 202 may comprise a discharge nozzle which is adaptedto be in fluid communication with the contents of a vial when such avial is inserted into the housing 202. In such a device a vial may beaccepted by the housing 202 such that the housing 202 provides thedischarge nozzle for expelling the pharmaceutical components. Further tothis the device 200 may further comprise an activator 105 adapted to actupon a discharge member to expel the contents of the vial through thedischarge nozzle. In this embodiment, the vial may be replaced whilstthe components of the device may be reused.

Now with reference to the devices shown in FIGS. 18 to 21, the device200 is configured to attach to packaging 136,142 containing a syringe144. The syringe 144 may be supplied in packaging 136, 142 which may beremoved before the pharmaceutical components are administered. Themixing event may be carried out with the aid of the device 200 beforethe packaging is removed. Using such a device 200, the syringe 144 neednot be removed from its packaging 136, 142 until the pharmaceuticalcomponents are actually to be administered.

Still with reference to FIGS. 18 to 21 the device 200 may furthercomprise at least one retaining member 138, 145 configured to retain thedevice 200 against the packaging 136, 112 containing a syringe 144. Thedevice 200 may include an element such as a latch, a side interferenceclip 138, or a return clip 145 which are configured to engage with acorresponding portion of the packaging 136, 142 of the syringe 144, forexample a detent or an edge of the packaging 136, 142. Alternatively oradditionally the device 200 may comprise an adhesive to retain thedevice 200 against the packaging 136, 142. Further, the device 200 maybe held against the packaging 136, 142 by application of a force by theuser.

The pharmaceutical components for mixing comprise at least two phases.The at least two phases may separate after a time of inactivity. Thecomponents may include more than two phases. As an example, in a casewhere there are two phases, both phases may be liquid phases or onephase may be a liquid phase whilst the other is a solid phase. In eithercase the components may be mixed by shaking the container in which theyare enclosed. In the case where there are three phases, there may be acombination of two liquid phases and one solid phase, one liquid phaseand two solid phases, or three liquid phases. A liquid phase maycomprise a component for suspension of a solid phase wherein the solidphase comprises a pharmaceutically active component. Alternatively oradditionally any liquid phase may also comprise a pharmaceuticallyactive component.

Further disclosure of various features is now described with referenceto the figures. Notably, FIG. 1A illustrates a schematic overview of theelectronic system that can be utilized with various embodimentsdescribed and illustrated herein. It is noted that for theseembodiments, the forces are measured preferably using a 3-axisaccelerometer 150 because the user's shaking movement will likely be inmore than one direction and furthermore sufficient acceleration may be afactor of accelerations in multiple directions. Hence, a threshold maybe determined to be a function of one or more acceleration directions.

Additionally the system may include a start switch 153, which may be amanually activated switch, or preferably may be an accelerationactivated switch to wake up the circuit, thus conserving battery powerwhen the device is not in use. The advantage of the accelerationactivated switch is that the user need only start shaking the device toswitch it on. In some embodiments it may be preferable to require theuser to make a conscious decision to switch the device on, and carry outa specific explicit action to switch the device on, hence the manualswitch may be preferable. Once the device has woken up, the batterylatch 152 ensures power is supplied from the battery 151 for sufficienttime to complete the shake cycle and provide feedback to the user.

A further development of this embodiment is described as follows. Timeis measured using a microcontroller 154, microprocessor or timer fromthe moment that shaking is first detected. The electronic system isprogrammed with an algorithm which compares the measured shakeacceleration and duration with a preset threshold. The electronic systemcompares the recorded elapsed time and force measurements and returns acommunication signal corresponding to the device state 155. The devicestate is communicated using one or preferably a combination of thefollowing: visual feedback such as light emitting diode (LED), graphicaldisplay such as Liquid Crystal Display (LCD); audible feedback such asan audible buzzer or polyphonic speaker; tactile feedback such asvibration motor. Such an electronic circuit requires a power source,such as a battery, that may be rechargeable or not. If not rechargeable,the battery may be replaceable or it may not be replaceable, in whichcase the device must be disposed of in its entirety at end of life,defined by the end of the battery life. If the battery is rechargeable,it may be replaceable or it may not be replaceable, in which case thedevice must be disposed of in its entirety at end of life, defined bythe end of life of the battery when it no longer holds enough charge tousefully power the device. This may be defined by a number of chargecycles.

The electronic circuit is contained inside the device, with visualfeedback means visible to the user by way of a window or lighttransmitting element. The electronic circuit affords additional designfeatures:

Pause Function.

The program may allow the system to detect when shaking has endedprematurely, or if the level of shaking vigor has reduced to a levelbelow the pre-set threshold, using the accelerometer or accelerationactivated switch. If such events are detected the device may enter apause mode, which pauses the timing process and may indicate to the userthat the device has entered pause mode. The indication to the user maybe a pause in the feedback being provided, such as a pause in theaudible tone, or a pause in die tactile vibration; or it may be by othermeans such as a state change on a light or screen. The user, uponreceiving the pause indication may then correct their actions, byrecommencing the shake action or increasing the vigor of the shakeaction, at which moment the device switches out of pause mode andrecommences with the timing and force monitoring process, starting fromthe time count at which it paused. If the device is in pause mode for asignificant amount of time such that the particles may have started tore-form a sediment, the timer will be reset. Reset of the timer may ormay not be indicated to the user via a user notification device. Thiscould for example be notified to the user by a message on a display, theemission of an audible tone, a tactile vibration or as a state change ona light or screen.

Syringe Administration Timer.

A timer may be used to warn the user that too much time has elapsedsince the device was shaken. After shaking, the particles will slowlyreturn to a sediment state; therefore there is a maximum time limitbetween shaking the device and administering the injection. In somescenarios, the user may shake the device correctly, but then may bedistracted long enough for the particles in the syringe to re-sediment.A timer may be set such that when the max allowable time after shakingof the housing has elapsed, the user is warned to shake the device againbefore administration. This warning could be communicated using severalmethods. As examples, an audible buzzer could sound when the maximumtime has elapsed, or a green light which was illuminated to indicateshaking has completed could switch off.

Low Battery Warning.

Such an electronic system requires a power source, preferably a batterycell. When the remaining power in the battery has reduced to a pointwhere device functionality may soon become impaired, the device mayindicate to the user that a battery failure is imminent, and that thebattery must be replaced. The device could shut down in such an event sothat it may not be used until the battery has been replaced. This wouldprevent a potential device malfunction. The state of the battery may bemeasured as the remaining charge or power in the battery, the voltagesupplied to the circuit, the current supplied to the circuit, or thestability of the battery under varying loads. Alternatively in the caseof a rechargeable battery the health of the battery may be monitored toindicate when device functionality may be impaired. If the devicenotifies the user that failure of the power source is imminent then theuser may take action to replace the battery or the whole device. In thecase where the battery is not replaceable, the finite lifetime of thebattery may be less than the lifetime of the other components, and maybeneficially indicate to the user that the device should be replacedbefore any other components reach their lifetime.

Error Warning.

Such an electronic system can perform self-checks on the system and maincomponents so that when errors are detected the user may be givenwarning. It can perform such self-checks whenever the device is awokenfor a shake cycle and immediately communicate that it has entered anerror mode. This prevents the user from using a faulty device andprompts them to take remedial action, for example to return the deviceto the manufacturer, and use a replacement device.

Information Distinguishing Force and Time.

In the first instance this invention is described as providing the userwith information on the success of the shake action as a single piece ofinformation, when both sufficient time AND sufficient vigor have beenachieved. An alternative arrangement of such an electronics system canprovide feedback to the user on the constituent elements; in that twopieces of information are provided, the elapsed time and the level ofvigor over that time. That way if a user fails to achieve thecombination of sufficient time and vigor they may consult theinformation provided and determine the reason they were unable to besuccessful, they may determine if they failed to shake for sufficienttime, or if they failed to shake with sufficient vigor.

Drug Expiration Alert.

A development of such an electronic system incorporates means to readthe expiration data on the syringe and warn the user if it has expired.If the user were informed that the expiration date had expired theycould dispose of the expired syringe and use another that had notexpired. Such a system uses scanning components that read a barcode ortext on the syringe to gather the expiration date, or may communicatewith a chip on the syringe that contains the lot and expirationinformation, and compares the date to an internal clock and calendarprogrammed into the processor and gives an alert if the gathered date isbefore that on the internal clock and calendar.

The features described and illustrated above can be embodied in thefollowing Embodiments 1-8 with highlights in the variations anddifferences between each embodiment described with reference to thedrawing figures indicated below.

Embodiment 1. Mimic

The trainer embodiment (FIG. 1B and FIG. 2) uses a form factor for ahousing that mimics that of a syringe. It may include a syringe barrelelement 103, with finger flange 100 at one end and a barrel tip 104 atthe other. The distance between finger flange 100 and barrel tip 104 aresimilar to that of a syringe such that it may be held in a similarfashion. At the top of the form is a cylindrical portion 100 thatrepresents a syringe plunger rod. The barrel 103 includes a lightemitting feedback window 102, through which light is emitted tocommunicate the state of the device. In the preferred embodiment, amberlight is used to indicate the device is running through a shake cycleand is monitoring the level of agitation imparted on it; green light isused to indicate the shake cycle is complete and sufficient shaking hasoccurred. When not in use, the light is off to conserve battery powerand also to indicate that the shake cycle has not yet commenced.

Embodiment 2—Attach

The embodiment shown in FIG. 3-FIG. 5 attaches to the syringe andprovides feedback to the user while they are shaking the syringe. Thedevice housing may include a body 109 with a slot 111 sized to accept asyringe barrel 107. A clip 112 (FIG. 4) in the slot 111 retains thesyringe. Once the device housing is attached to a syringe, the shakingmotion is measured using the internal electronic system, and the devicestate is communicated in two simultaneous ways. The first communicationmethod is with light emitted from the light emitting feedback window110. An amber light indicates that a shake cycle is in progress, and agreen light indicates that it is completed. The second simultaneousfeedback method is audible. An intermittent audible buzzing toneindicates that the shake cycle is in progress, which changes to acontinuous tone when the shake cycle is completed. Furthermore, theintermittent tone emitted during the shake cycle is set at a frequencyof approximately 3 Hz to reinforce the frequency and speed of shakerequired for optimum mixing, exploiting the tendency for humans to matchrepetitive behavior to percussive audible tones.

Embodiment 3—Case

The embodiment shown in FIG. 6-FIG. 9 contains the syringe and providesfeedback to the user while they are shaking the syringe. The devicehousing is opened by pressing on the lid catch 120; a syringe 117 isplaced in the case liner 115 where it is retained by a spring clip 118as shown in FIG. 7. Alternatively, the syringe could be retained by caselid 113 when the device housing is closed. Case lid 113 pivots aroundthe case syringe 116 enclosing the syringe as shown in FIG. 8. The caseincludes flat surfaces on the case base 148 and case top 149 (FIG. 9),such that when placed on a desktop or work top it will not roll off. Thecase is closed and retained in a closed position by the lid catch 120.The outer shape of the case is designed to allow for users to hold itcomfortably and securely when shaking. Shaking motion is measured usingthe internal electronic system, and the device state is communicated intwo simultaneous ways. The first communication method is with lightemitted from the light emitting panel 119, and amber light indicatesthat a shake cycle is in progress; and a green light indicates that itis completed. The second simultaneous feedback method is tactile. Anintermittent vibration transmitted to the holding hand indicates thatthe shake cycle is in progress which changes to a continuous vibrationwhen the shake cycle is completed. Furthermore the intermittentvibration emitted during the shake cycle is set at a frequency ofapproximately 3 Hz to reinforce the frequency and speed of shakerequired for optimum mixing, exploiting the tendency for humans to matchrepetitive behavior to percussive stimuli. The light emitting panelturning green indicates to the user to remove the syringe and continuewith the drug administration process. This embodiment may be furtherdeveloped with a syringe lock out feature. This feature would detect thepresence of the syringe inside, lock the case in the closed state andonly unlock the case when sufficient time and shake vigor have beenachieved. In addition, if the user does not open the case to remove thesyringe for injection within a specified time period, the case couldre-lock itself and/or the light could turn amber again, indicating thatthe device housing must be shaken again to re-suspend the particlesbefore the syringe can be used.

Embodiment 4—Pot

The embodiment shown in FIG. 10 and FIG. 11 includes an elongated bodyhousing approximately the same length as the syringe barrel. The syringeis inserted into a syringe receiving hole 123 in the body housing and isretained by the compressive force applied by the fingers between thesyringe finger flange 101 and the device body housing base 124. When thecoupled device and syringe are shaken, motion is measured using theinternal electronic system, and the device state is communicated in twosimultaneous ways. The first communication method is with light emittedfrom the light emitting band 122, and amber light indicates that a shakecycle is in progress; and a green light indicates that it is completed.The second simultaneous feedback method is tactile. An intermittentvibration transmitted to the holding hand indicates that the shake cycleis in progress which changes to a continuous tone when the shake cycleis completed. Furthermore, the intermittent vibration emitted during theshake cycle is set at a frequency of approximately 3 Hz to reinforce thefrequency and speed of shake required for optimum mixing, exploiting thetendency for humans to match repetitive behavior to percussive stimuli.The light emitting panel turning green indicates to the user to removethe syringe and continue with the drug administration process. As withother embodiments, further means of supplemental communication may beincluded, such as audible or tactile vibrating feedback, and a timingfunction can be used to signal the user if the syringe has not beenremoved from the device before a specified time period, indicating thatthe device must be shaken again to re-suspend the particles prior toperforming the injection. A switch internal to receiving hold 123 wouldbe used to detect when the syringe is attached to the device.

Embodiment 5—Finger Rest Attachment

The embodiment shown in FIG. 12, FIG. 13 and FIG. 14 is similar toembodiment 2, in that it attaches to the syringe. It is shown on thesyringe in FIG. 13 and FIG. 14. The syringe fits and is retained in thesyringe accepting slot 125. The electronic system is housed within, andcommunicates to the user via the light panel 126 on the front face. Anorange color indicates when the device is sensing and this turns greenwhen it has been shaken sufficiently. As with other embodiments, furthermeans of supplemental communication may be included, such as audible ortactile vibrating feedback.

Embodiment 6—Puck

The embodiment shown in FIG. 15 and FIG. 16 is similar to embodiment 4,in that it fits to the bottom of the syringe but is a much more compactdesign. It may include a body housing 127 with syringe accepting hole128. The interface is provided by a circumferential light emitting band129 around the diameter of the base of the form. In use, the syringe isinserted into the syringe accepting hole 128 and is held in place withthe user's thumb on the underside thumb grip 130. As with otherembodiments, further means of supplemental communication may beincluded, such as audible or tactile vibrating feedback.

Embodiment 7—Evoke

The embodiment shown in FIG. 17 is similar to embodiment 1 of FIGS. 1Band 2. It is a stand-alone device, which does not interact with thesyringe, intended to be used in advance of the administration process.The user may practice shaking in advance of shaking the real syringe. Itmay include the device body housing 134, at either end of is the fingergrip 131 and the thumb grip 132. The distance between finger grip andthumb grip is similar to the distance between the syringe finger gripand rubber stopper, to ensure it feels similar in the hand. When theuser shakes the device, the device detects the forces applied and emitsan amber light from the light emitting window 133. The light turns greenwhen sufficiently vigorous shaking has occurred for sufficient time. Aswith other embodiments, further means of supplemental communication maybe included, such as audible or tactile vibrating feedback.

Embodiment 8—Packaging B

With reference to FIG. 20 and FIG. 21, this embodiment is similar toembodiment 8, in that the device 141 attaches to the syringe blisterpackaging 142 while the syringe 144 is contained within. In thisembodiment, the protective film 143 is still in place on top of theblister tray 142. With reference to FIG. 21 the device is attached tothe blister tray by sliding it along the length of the blister tray andis retained against the blister tray by means of return clips 145 on theunderside of the device. The body housing of the device 147 includesmeans of communication, a light emitting strip 146. As with otherembodiments the electronic system in the device detects the onset ofshaking and starts to monitor the vigor and duration of shaking. Whiledoing so, the light emitting strip 146 emits amber light. Oncesufficient vigor and duration have been achieved the light changes togreen. After shaking is completed the device is removed from the blistertray 142; the blister tray film 143 is peeled off and the device is usednormally as per the syringe administration instructions. As with otherembodiments, further means of supplemental communication may beincluded, such as audible or tactile vibrating feedback.

It is noted that during formulation development for Invega SustennaThree Month, the required duration and vigor required were identifiedand quantified as 15 seconds of vigorous shaking. Vigorous shaking wasinitially defined using a training video in which an expert experiencedin the correct preparation of the pharmaceutical product shakes asyringe for the required 15 seconds at the required level of vigor.Video analysis was used to estimate the amplitude and frequency of thedemonstrated shake, finding that shake amplitude of approximately 40 cmwas used at a frequency of 3.4 hertz. Assuming simple harmonic motion itwas calculated that the syringe was experiencing a maximum accelerationof 9.3 g. This provides an indication of the required accelerationsimparted on the fluid to achieve sufficient mixing as recommended by anexpert in the preparation of such a formulation.

The failure mode associated with not mixing the syringe sufficiently isa failure to administer the full dose from the syringe. This occursbecause insufficiently shaken syringes contain residual sediment whichcan block, or partially block, the syringe or needle duringadministration. Therefore syringes containing fluids with differentsediment properties such as mass, density, and concentration can bequantified in terms of the required mixing vigor by applying controlledand known levels of acceleration (by experimental means) measuring theforce required to eject the fluid from a syringe. Using such methods,different shake vigor thresholds may be determined for different fluidwith different properties. FIG. 22 illustrates the device requirementfor a threshold exceeding the intrinsic variability in the devicepopulation.

Once the required threshold is determined, the behavior of users shouldalso be understood. Different users will have different capabilities,strengths, habits and expectations; therefore, there is in inherentvariability in the way each interprets the instruction “shakevigorously” and some will naturally fail to meet the required thresholdas illustrated in the chart in FIG. 23. Moreover, different users employdifferent shaking techniques, which some of which will be more vigorousthan others. Acknowledging this variability, and that a minimum shaketime and vigor are required leads to the conclusion that a need existsfor the device described in this disclosure. The device can communicatethe required time and vigor to the user, and modify behavior, increasingthe likelihood of the user achieving the minimum required level ofmixing. The subsequent effect of the device on the behavior across apopulation of users is illustrated in FIG. 24.

Once the threshold requirements and behavior modification goals areunderstood, consideration can be given to the various embodiments ofform and function that might elicit the desired behavior modification.Such embodiments may either be used as a stand-alone device or as an inprocess device.

A stand-alone device is used in isolation of the administration process,providing the user an opportunity to shake a device and learn what levelof vigor is required when they come to shake the real device. Such astand-alone device may have a form factor close to that of the syringeso it may represent the experience of shaking the real syringe a closelyas possible. Other form factors may also be used. For example, if thedrug comes in a vial, a vial shaped device would be more appropriate.

An assistive device is required to couple with, attach to, or encase thereal syringe. As such means of coupling, attaching or encasing arerequired. This leads to varied opportunities for several form factorsillustrated in FIGS. 1-21. Several means of communicating the devicestate to the user are possible. As previously described, they mayinclude lights of different color or state (flashing or steady state);they may include audible means such as buzzers and speakers; and theymay include tactile means such as vibrations. Further means are possibleas shown in FIG. 25, such as a LCD 301 (liquid Crystal Display) orsimilar, which may use graphical means to communicate the device state.An LCD may be used as a segment display to communicate device statethrough words and icons, or it may be used as a metaphorical indicationof the mix state of the solution such as described in FIG. 26. In thiscase, LCD segments or pixels are switched on or off to create a visualindication of particles mixing with solution. On the left side 302 ofFIG. 26, darkly colored pixels in the lower portion of the displayrepresent the presence of sediment in the bottom of the syringe. Whenshaking is detected by the electronic system, different pixels areswitched on and off across the whole screen to indicate mixing is inprogress, and when sufficient mixing is achieved the LCD can show auniform homogenous color across the whole screen, indicating that thesolution is also in a uniform homogeneous state. In order, as the deviceis shaken and the mixing progresses from the first state 302 indicatingthat sediment will be present, switching different pixels on and offacross the screen the state progresses through the second state 303. Asshaking and mixing continues, fewer pixels are turned on and the screenappears more sparse of pixels in the third state 304, until the wholescreen is homogeneous in a final state 305.

By virtue of various embodiments of the invention, certain benefits wererealized where the invention is configured as a stand-alone trainingdevice: (a) It makes the user aware of what the required shake time is;they learn through experience, (h) It allows the user to experience whatthe required level of shake vigor is, (c) It teaches the user whatduration and level of vigor is required for the real device withoutimpeding the normal administration process flow (d), It allows a deviceto have a form factor very close to that of the real syringe, (e), Itallows the user to develop their skills so they are able to shakesyringe sufficiently without having to rely on assistive aids, and (f)It is independent of the actual injection process and thus does notoverly complicate it.

Other benefits were also realized when the invention is configured as anactual or “in-process” device: (a) It makes the user aware of what therequired shake time is; they learn through experience, (b) It allows theuser to experience what the required level of shake vigor is, (c) Whenattached to the syringe it allows the actual syringe to be shaken,providing the user with real time reassurance that it has been shakenadequately, and (d) If used correctly it reduces the chance of a realsyringe being shaken insufficiently.

It is noted that these embodiments have been prototyped for testing withmultiphase injectable pharmaceutical solutions. From such testing, aversion has been selected for commercialization with a product with thetrademark of INVEGA TRINZA™, which product is planned for distributionby Janssen Pharmaceuticals, Inc. Titusville, N.J. 08560. It is alsonoted that the proposed commercial version of the invention is intendedto be utilized with INVEGA TRINZA™ which is described in further detailbelow.

In one particular embodiment, a device for training users in a propermixing of pharmaceutical components is provided including a housing thatextends along a longitudinal axis and containing an electronic system asshown in FIG. 1A. A battery is disposed in the housing for providingpower to the device. The device includes a 3-axis accelerometer formeasuring the spatial acceleration or forces applied to the device. The3-axis accelerometer allows the measurement of a user's shaking movementin more than one direction. Additionally, an acceleration activatedstart switch is provided to wake up the device when a user has startedto shake the device. A battery latch is connected to the battery so asto ensure that once the device has woken up, power is supplied from thebattery for sufficient time to complete a shake cycle and providefeedback to the user. A microcontroller is provided in the device, andconnected to the acceleration activated switch, the 3-axis accelerometerand the battery latch. Time is measured using the microcontroller, fromthe moment that shaking is first detected. The electronic system isprogrammed with an algorithm which compares the measured shakeacceleration and duration with a preset threshold. The electronic systemcompares the recorded elapsed time and force measurements and returns acommunication signal corresponding to the device state. Further, thedevice is provided with at least one light emitting diode (LED) forvisual feedback and a vibration motor for tactile feedback. Theelectronic system is contained inside the device, and the visualfeedback is made visible to the user by way of a window or lighttransmitting element.

In use, the user activates the device by beginning to shake the device.The microcontroller measures the elapsed time. Whilst the user isshaking the device, accelerations are measured using the 3-axisaccelerometer. The microcontroller determines by the algorithm, whetherthe level of shaking vigor is above a pre-set threshold. Whilst a shakecycle is in progress, an amber light emitted from the LED indicatesthis. Also, during a shake cycle the vibration motor emits anintermittent audible buzzing tone. The intermittent tone is set at afrequency of approximately 3 Hz to reinforce the frequency and speed ofshake required for optimum mixing.

If the level of shaking vigor applied by the user drops to a level belowthe pre-set threshold, then the electronic system detects this using the3-axis accelerometer. If this event has been detected, then the deviceenters a pause mode, which pauses the timing process and indicates tothe user that the device has entered the pause mode. This indication tothe user is provided by pausing the tactile vibration from the vibrationmotor. Upon receiving the pause indication, the user may then correcttheir actions, by recommencing the shake action or increasing the vigorof the shake action such that the level of shaking vigor is above apre-set threshold. At this moment, the device switches out of pause modeand recommences with the timing and acceleration monitoring process. Inthis case, the time count starts from the time count at which the devicewas paused. If the device is in pause mode for a significant amount oftime, such that the particles may have started to re-form a sediment,the timer will be reset.

Once the user has achieved sufficient vigor and time of shaking, theelectronic system determines that the shake cycle is completed. Thecompletion of the shake cycle is indicated to the user by emitting agreen light from the LED. The completion of the shake cycle is alsoindicated to the user by the vibration motor emitting a continuous tone.

Once the shaking cycle has been completed successfully, a timer beginsto count to ensure that too much time does not elapse between theshaking of the device and the administration of the injection. The timeris set such that when a maximum allowable time after shaking the housinghas elapsed, the user is warned to shake the device again beforeadministration. The timer may be set, for example, to warn the userafter five minutes of inaction after shaking the housing. An indicationto the user that the maximum time has elapsed is given by switching offthe green light from the LED which previously indicated that the shakecycle was completed.

When the power remaining in the battery reaches a low enough level, suchthat the functionality of the device may soon become impaired, thedevice is configured to indicate to the user that a battery failure isimminent. At this point the user may replace the battery. In the eventwhere the electronic system has detected that the power level in thebattery is too low, the device is shut down, such that it may not beused until the battery has been replaced.

Upon being awoken by the user in preparation for a shake cycle, theelectronic system performs self-checks on the system and the maincomponents, such as the 3-axis accelerometer. If the electronic systemdetermines the device to be faulty, an error mode is entered and this iscommunicated to the user through the LED or the vibration motor. Thisprevents the user from using a faulty device and prompts them to takeremedial action.

Referring to FIG. 27, further information about the mixing ofpharmaceutical components forming part of this disclosure is providedbelow.

Indications and Usage

INVEGA TRINZA™ (paliperidone palmitate), a 3-month injection, isindicated for the treatment of schizophrenia in patients after they havebeen adequately treated with INVEGA SUSTENNA® (1-month paliperidonepalmitate extended-release injectable suspension) for at least fourmonths [see Dosage and Administration (2.2) and Clinical Studies (14)].

Dosage and Administration

2.1 Administration Instructions

INVEGA TRINZA™ should be administered once every 3 months.

Each injection must be administered only by a health care professional.

Parenteral drug products should be inspected visually for foreign matterand discoloration prior to administration. It is important to shake thesyringe vigorously for at least 15 seconds to ensure a homogeneoussuspension. Inject INVEGA TRINZA™ within 5 minutes of shaking vigorously[see Dosage and Administration (2.8)].

INVEGA TRINZA™ is intended for intramuscular use only. Do not administerby any other route. Avoid inadvertent injection into a blood vessel.Administer the dose in a single injection; do not administer the dose individed injections. Inject slowly, deep into the deltoid or glutealmuscle.

INVEGA TRINZA™ must be administered using only the thin wall needlesthat are provided in the INVEGA TRINZA™ pack. Do not use needles fromthe 1-month paliperidone palmitate extended-release injectablesuspension pack or other commercially-available needles to reduce therisk of blockage.

Deltoid Injection

The recommended needle size for administration of INVEGA TRINZA™ intothe deltoid muscle is determined by the patient's weight:

-   -   For patients weighing less than 90 kg, the 1-inch, 22 gauge thin        wall needle is recommended.    -   For patients weighing 90 kg or more, the 1½-inch, 22 gauge thin        wall needle is recommended.

Administer into the center of the deltoid muscle. Deltoid injectionsshould be alternated between the two deltoid muscles.

Gluteal Injection

Regardless of patient weight, the recommended needle size foradministration of INVEGA TRINZA™ into the gluteal muscle is the 1½-inch,22 gauge thin wall needle. Administer into the upper-outer quadrant ofthe gluteal muscle. Gluteal injections should be alternated between thetwo gluteal muscles.

Incomplete Administration

To avoid an incomplete administration of INVEGA TRINZA™, ensure that theprefilled syringe is shaken vigorously for at least 15 seconds within 5minutes prior to administration to ensure a homogeneous suspension andensure the needle does not get clogged during injection/see Dosage andAdministration (2.8)].

However, in the event of an incompletely administered dose, do notre-inject the dose remaining in the syringe and do not administeranother dose of INVEGA TRINZA™. Closely monitor and treat the patientwith oral supplementation as clinically appropriate until the nextscheduled 3-month injection of INVEGA TRINZA™.

2.2 Schizophrenia

Adults

INVEGA TRINZA™ is to be used only after INVEGA SUSTENNA® (1-monthpaliperidone palmitate extended-release injectable suspension) has beenestablished as adequate treatment for at least four months. In order toestablish a consistent maintenance dose, it is recommended that the lasttwo doses of INVEGA SUSTENNA® be the same dosage strength beforestarting INVEGA TRINZA™.

Initiate INVEGA TRINZA™ when the next 1-month paliperidone palmitatedose is scheduled with an INVEGA TRINZA™ dose based on the previous1-month injection dose, using the equivalent 3.5-fold higher dose asshown in Table 1. INVEGA TRINZA™ may be administered up to 7 days beforeor after the monthly time point of the next scheduled paliperidonepalmitate 1-month dose.

TABLE 1 INVEGA TRINZA ™ Doses for Adult Patients Adequately Treated withINVEGA SUSTENNA ® If the Last Dose of Initiate INVEGA TRINZA ™ INVEGASUSTENNA ® is: at the Following Dose:  78 mg 273 mg 117 mg 410 mg 156 mg546 mg 234 mg 819 mg Conversion from the INVEGA SUSTENNA ® 39 mg dosewas not studied.

Following the initial INVEGA TRINZA™ dose, INVEGA TRINZA™ should beadministered every 3 months. If needed, dose adjustment can be madeevery 3 months in increments within the range of 273 mg to 819 mg basedon individual patient tolerability and/or efficacy. Due to thelong-acting nature of INVEGA TRINZA™, the patient's response to anadjusted dose may not be apparent for several months [see ClinicalPharmacology (12.3)].

2.3 Missed Doses

Dosing Window

Missing doses of INVEGA TRINZA™ should be avoided. If necessary,patients may be given the injection up to 2 weeks before or after the3-month time point.

Missed Dose 3½ Months to 4 Months Since Last Injection

If more than 3½ months (up to but less than 4 months) have elapsed sincethe last injection of INVEGA TRINZA™, the previously administered INVEGATRINZA™ dose should be administered as soon as possible, then continuewith the 3-month injections following this dose.

Missed Dose 4 Months to 9 Months Since Last Injection

If 4 months up to and including 9 months have elapsed since the lastinjection of INVEGA TRINZA™, do NOT administer the next dose of INVEGATRINZA™. Instead, use the re-initiation regimen shown in Table 2.

TABLE 2 Re-initiation Regimen After Missing 4 Months to 9 Months ofINVEGA TRINZA ™ Administer Then administer INVEGA SUSTENNA ®, INVEGATRINZA ™ If the Last two doses one week apart (into deltoid^(a) Dose ofINVEGA (into deltoid muscle) or gluteal muscle) TRINZA ™ was: Day 1 Day8 1 month after Day 8 273 mg  78 mg  78 mg 273 mg 410 mg 117 mg 117 mg410 mg 546 mg 156 mg 156 mg 546 mg 819 mg 156 mg 156 mg 819 mg ^(a)SeeInstructions for Use for deltoid injection needle selection based onbody weight.

Missed Dose Longer than 9 Months Since Last Injection

If more than 9 months have elapsed since the last injection of INVEGATRINZA™, re-initiate treatment with the 1-month paliperidone palmitateextended-release injectable suspension as described in the prescribinginformation for that product. INVEGA TRINZA™ can then be resumed afterthe patient has been adequately treated with the 1-month paliperidonepalmitate extended-release injectable suspension for at least 4 months.

2.4 Use with Risperidone or with Oral Paliperidone

Since paliperidone is the major active metabolite of risperidone,caution should be exercised when INVEGA TRINZA™ is coadministered withrisperidone or oral paliperidone for extended periods of time. Safetydata involving concomitant use of INVEGA TRINZA™ with otherantipsychotics is limited.

2.5 Dosage Adjustment in Renal Impairment

INVEGA TRINZA™ has not been systematically studied in patients withrenal impairment [see Clinical Pharmacology (12.3)]. For patients withmild renal impairment (creatinine clearance 50 mL/min to <80 mL/min[Cockcroft-Gault Formula], adjust dosage and stabilize the patient usingthe 1-month paliperidone palmitate extended-release injectablesuspension, then transition to INVEGA TRINZA™ [see Table 1, Dosage andAdministration (2,2)]. [See also Use in Specific Populations (8.6) andClinical Pharmacology (12.3)]

INVEGA TRINZA™ is not recommended in patients with moderate or severerenal impairment (creatinine clearance <50 mL/min) [see Use in SpecificPopulations (8.6) and Clinical Pharmacolo, (12.3)].

2.6 Switching from INVEGA TRINZA™ to the 1-Month Paliperidone PalmitateExtended-Release Injectable Suspension

For switching from INVEGA TRINZA™ to INVEGA SUSTENNA® (1-monthpaliperidone palmitate extended-release injectable suspension), the1-month paliperidone palmitate extended-release injectable suspensionshould be started 3 months after the last INVEGA. TRINZA™ dose, usingthe equivalent 3.5-fold lower dose as shown in Table 3. The 1-monthpaliperidone palmitate extended-release injectable suspension shouldthen continue, dosed at monthly intervals.

TABLE 3 Conversion From INVEGA TRINZA ™ to INVEGA SUSTENNA ® If the LastDose of Initiate^(a) INVEGA SUSTENNA ® INVEGA TRINZA ™ is: 3 MonthsLater at the Following Dose: 273 mg  78 mg 410 mg 117 mg 546 mg 156 mg819 mg 234 mg ^(a)The initiation dosing as described in the prescribinginformation for INVEGA SUSTENNA ® is not required.

2.7 Switching from INVEGA TRINZA™ to Oral Paliperidone Extended-ReleaseTablets

For switching from INVEGA TRINZA™ to oral paliperidone extended-releasetablets, the daily dosing of the paliperidone extended-release tabletsshould be started 3 months after the last INVEGA TRINZA™ dose andtransitioned over the next several months following the last INVEGATRINZA™ dose as described in Table 4, Table 4 provides dose conversionregimens to allow patients previously stabilized on different doses ofINVEGA TRINZA™ to attain similar paliperidone exposure with once dailypaliperidone extended-release tablets.

TABLE 4 INVEGA TRINZA ™ Doses and Once-Daily PaliperidoneExtended-Release Conversion Regimens Needed to Attain SimilarPaliperidone Exposures Last Weeks Since Last INVEGA TRINZA ™ Dose INVEGA3 months to Longer than 18 Longer than TRINZA ™ 18 weeks weeks to 24weeks 24 weeks Dose Doses of oral paliperidone extended-release tablets273 mg 3 mg 3 mg 3 mg 410 mg 3 mg 3 mg 6 mg 546 mg 3 mg 6 mg 9 mg 819 mg6 mg 9 mg 12 mg 

2.8 Instructions for Use

-   -   Administer every 3 months    -   Shake syringe vigorously for at least 15 seconds (see FIG. 27)

For intramuscular injection only. Do not administer by any other route.

INVEGA TRINZA™ should be administered by a healthcare professional as asingle injection. DO NOT divide dose into multiple injections.

INVEGA TRINZA™ is intended for intramuscular use only. Inject slowly,deep into the muscle taking care to avoid injection into a blood vessel.

Read complete instructions prior to use.

Dosing

This medication should be administered once every 3 months.

Preparation

Peel off tab label from the syringe and place in patient record.

INVEGA TRINZA™ requires longer and more vigorous shaking than INVEGASUSTENNA® (1-month paliperidone palmitate extended-release injectablesuspension). Shake the syringe vigorously, with the syringe tip pointingup, for at least 15 seconds within 5 minutes prior to administration(see Step 2).

In addition to the embodiments and disclosure provided above, which maybe claimed individually, separately, in part or in combination, withfeatures from the entire disclosure provided herein, the followingnumbered embodiments may be claimed individually, separately, in part orin combination, with features from the entire disclosure providedherein:

1. A device for training users in a proper mixing of pharmaceuticalcomponents or a device for aiding in the mixing and administration ofpharmaceutical components, or a device for mixing and administeringpharmaceutical components, the device comprising:

-   -   a housing for receiving a pharmaceutical delivery device        containing the pharmaceutical components;    -   a microcontroller disposed in the housing; and    -   a motion/orientation detection device disposed within or on the        lousing and in communication with the microcontroller.

2. The device of numbered embodiment 1, wherein the motion/orientationdetection device is electrically connected to the microcontroller.

3. The device of any one of the preceding numbered embodiments, whereinthe motion/orientation detection device comprises a device configured todetect one or both of: motion; and orientation of the housing withrespect to the ground.

4. The device of any one of the preceding numbered embodiments, whereinthe motion/orientation detection device is configured to detect a motionof the housing and provide a signal indicative of such motion to themicrocontroller.

5. The device of any one of the preceding numbered embodiments, whereinthe motion/orientation detection device is configured to detect anorientation of the housing and provide a signal indicative of suchorientation to the microcontroller.

6. The device of any one of the preceding numbered embodiments, furthercomprising a user notification device.

7. The device of numbered embodiment 6, wherein the user notificationdevice comprises one or more of: a display, a tactile feedback unit, alight emitting device and/or a vibratory alert unit.

8. The device of numbered embodiment 6 or numbered embodiment 7, whereinthe user notification device is mounted on an external surface of thehousing for notifying a user as to its status.

9. The device of any one of the preceding numbered embodiments whendependent on any one of numbered embodiments 6 to 8, wherein themicrocontroller is configured to indicate via the user notificationdevice as to whether the motion and/or orientation of the housing beingshaken during one of a drug mixing and administration, or a trainingevent, is sufficient enough for satisfactory mixing of thepharmaceutical components fix delivery.

10. The device of numbered embodiment 9, wherein the user notificationdevice is a display and the microcontroller is configured to indicatevia the display the state of mixing of the pharmaceutical components ina real-time manner.

11. The device of numbered embodiment 10, wherein the microcontroller isconfigured to change progressively the color and or pattern of one ormore display elements on the display as shaking takes place untilsufficient shaking has taken place for satisfactory mixing of thepharmaceutical components for delivery.

12. The device of numbered embodiment 10, wherein the microcontroller isconfigured to display two types of display elements on the display whichare grouped together in two discrete portions of the display prior tocommencement of shaking, and which progressively mix which each other onthe display so long as shaking continues at a sufficient enough orpre-defined force and/or for a sufficient enough or predefined duration,until such time that it is determined that sufficient shaking has takenplace for satisfactory mixing of the pharmaceutical components fordelivery, at which time the two types of display elements are whollyintegrated with each other in a regular pattern across the display.

13. The device of any one of numbered embodiments 9 to 12, wherein themicrocontroller is configured to determine whether there is satisfactorymixing with respect to one or more predetermined thresholds includingmagnitude of the force applied during shaking, the orientation of thehousing and duration of such shaking.

14. The device of any one of the preceding numbered embodiments, whereinthe movement/orientation detection device comprises an accelerometer.

15. The device of numbered embodiment 14, wherein the accelerometercomprises a 3-axis accelerometer.

16. The device of any one of the preceding numbered embodiments, furthercomprising a power source disposed in the housing.

17. The device of numbered embodiment 16, wherein the microcontrolleris, when active, electrically powered by the power source.

18. The device of any one of the preceding numbered embodiments, furthercomprising a start switch electrically connected to the microcontroller.

19. The device of numbered embodiment 18, wherein the start switch isconfigured to activate the microcontroller from a power conservationmode into an active mode upon detection of movement of the housingduring one of a drug mixing and administration event, or a trainingevent.

20. The device of numbered embodiment 19, wherein the microcontroller isconfigured, during the power conservation mode, to draw reduced powerwith respect to the active mode, or no power at all, from the powersource.

21. The device of any one of numbered embodiments 18 to 20, wherein thestart switch is the motion/orientation detection device.

22. The device of any one of numbered embodiments 18 to 20, wherein thestart switch is separate to the motion/orientation detection device.

23. The device of any one of the preceding numbered embodiments, whereinthe microcontroller is configured to detect, during one of a drug mixingand administration or a training event, when shaking of the housing hasended prematurely for sufficient enough mixing of the components, or ifthe level of shaking vigor of the housing has reduced to a level below apre-set threshold for sufficient enough mixing of the components, and,if so, to enter a pause mode to restart shaking.

24. The device of numbered embodiment 23, wherein the pause mode isnotified to the user via the user notification device.

25. The device of any one of the preceding numbered embodiments, whereinthe microcontroller is configured, during one of a drug mixing andadministration or a training event, to set a timer and determine when amaximum allowable time has elapsed after sufficient shaking of thehousing has completed, and is configured, if the maximum allowable timehas elapsed to warn a user via the user notification device to shake thedevice again.

26. The device of any one of the preceding numbered embodiments, whereinthe housing extends along a longitudinal axis of the device.

27. The device of any one of the preceding numbered embodiments, whereinthe pharmaceutical delivery device comprises a syringe or vial.

28. The device of numbered embodiment 27, when dependent on numberedembodiment 26, wherein the housing comprises a syringe barrel elementwith finger flange and one end and a barrel tip spaced apart along thelongitudinal axis.

29. The device of any one of numbered embodiments 27 or 28, when thehousing comprises a body with a slot sized to accept a syringe barrel ora vial containing the pharmaceutical components.

30. The device of numbered embodiment 29, wherein the slot is alignedwith the longitudinal axis of the housing, and the longitudinal axis ofthe syringe barrel or the vial.

31. The device of any one of numbered embodiments 27 to 30, wherein thehousing is provided with a compartment and a lid to receive an entiresyringe or vial.

32. The device of numbered embodiment 31, wherein the compartment isdimensioned to receive the entire syringe or vial snugly and hold itsecurely within the housing.

33. The device of any one of numbered embodiments 27 to 32, wherein thehousing comprises an elongated body approximately the same, or slightlygreater than the length of a syringe barrel, such that a syringe isinserted into a syringe receiving hole in the body and retained by thecompressive force applied by the finger-like members between a syringefinger flange and a body base.

34. The device of any one of numbered embodiments 27 to 33 wherein thehousing comprises a body with a syringe accepting slot sized to accept asyringe barrel.

35. The device of any one of numbered embodiments 27 to 34 wherein thehousing comprises a puck-like body with a syringe accepting hole sothat, in use, a syringe is inserted into the syringe accepting hole andis held in place with a user's thumb on an underside thumb grip.

36. The device of any one of numbered embodiments 27 to 35 wherein thehousing comprises an opening through which a discharge nozzle of thesyringe or vial extends, or comprises an opening through which at leasta portion of the syringe barrel adjacent the syringe's discharge nozzlecan extend.

37. The device of any one of numbered embodiments 27 to 35 wherein thehousing comprises a discharge nozzle which is adapted to be in fluidcommunication with the contents of a vial when such a vial is insertedinto the housing.

38. The device of any one of numbered embodiments 27 to 35 wherein thesyringe comprises a discharge member adapted upon application of forcethereto to discharge the contents of the syringe.

39. The device of numbered embodiment 38, wherein the device furthercomprises an activator adapted to act upon the discharge member of thesyringe, or act on the vial, to expel its contents through the dischargenozzle.

40. The device of numbered embodiment 38, wherein the housing furthercomprises an activator opening through which the discharge member of thesyringe can extend for application of force directly by user fromoutside the housing.

41. The device of numbered embodiment 27, wherein the device is anattachment for a syringe and the housing is adapted to fit around abarrel of the syringe.

42. The device of numbered embodiment 41, wherein the housing is adaptedto fit around only a portion of the barrel of the syringe.

43. The device of numbered embodiment 41 or 42, wherein the housing isformed of two hinged portions which rotate in a hinged manner withrespect to each other, such that the hinged portions can close aroundthe barrel and latch thereto.

44. The device of any one of the preceding numbered embodiments whendependent on any one of numbered embodiments 16 to 22, wherein themicrocontroller is configured to detect low remaining power availabilityof the power source.

45. The device of numbered embodiment 44, wherein, when themicrocontroller detects a low remaining power availability of the powersource, it performs one or more of the following:

-   -   issues an alert representative of the low remaining power        availability to the user, for example via a user notification        device; and    -   prevents activation of the pharmaceutical delivery device for        delivery of the pharmaceutical components to a user.

46. The device of any one of the preceding numbered embodiments, whereinthe microcontroller is configured to detect an fault in the functioningof the device, for example in one or more of the motion/orientationdetection device, the housing or its attachment to or containment of thepharmaceutical delivery device.

47. The device of numbered embodiment 46, wherein, when themicrocontroller detects the error, it performs one or more of thefollowing:

-   -   issues an alert representative of the error to the user, for        example via a user notification device; and    -   prevents activation of the pharmaceutical delivery device for        delivery of the pharmaceutical components to a user.

48. The device of any one of the preceding numbered embodiments, furthercomprising a delivery device identification unit in communication withthe microcontroller.

49. The device of numbered embodiment 48, wherein the delivery deviceidentification unit is configured to read data on data storage means ofthe delivery device characteristic, of the pharmaceutical componentscontained therein and/or delivery device itself.

50. The device of numbered embodiment 49, wherein the data comprises oneor more of:

-   -   expiration date of the pharmaceutical components, whereby the        microcontroller is configured to alert a user via a user        notification device of the device if the current date as        determined by the microcontroller exceeds the expiration date;    -   data identifying the pharmaceutical components contained within        the delivery device, for example data indicative of manufacturer        or composition of the pharmaceutical components, whereby the        microcontroller is configured to alert a user via a user        notification device of the device if the data identifying the        pharmaceutical components does not match or sufficiently        correspond to permitted pharmaceutical components as stored in        the microcontroller or in memory connected thereto;    -   expiration date of the pharmaceutical components, whereby the        microcontroller is configures to prevent activation of the        pharmaceutical delivery device for delivery of the        pharmaceutical components to a user if the current date as        determined by the microcontroller exceeds the expiration date;        and    -   data identifying the pharmaceutical components contained within        the delivery device, for example data indicative of manufacturer        or composition of the pharmaceutical components, whereby the        microcontroller is configured to prevent activation of the        pharmaceutical delivery device for delivery of the        pharmaceutical components to a user if the data identifying the        pharmaceutical components does not match or sufficiently        correspond to permitted pharmaceutical components as stored in        the microcontroller or in memory connected thereto.

51. A method to direct a user on a proper g mixing technique with thedevice of any one of claims 1 to 50, the method comprising at least stepof determining motion and/or orientation of the housing.

52. A device according to any one of claims 1 to 50, wherein one of thepharmaceutical components comprise an active pharmaceutical substancewhich is INVEGA TRINZA™ (see Appendix; section 11).

53. A device according to any one of claims 1 to 50, wherein one of thepharmaceutical components comprise an active pharmaceutical substancewhich comprises a racemic mixture of (+)- and (−)-paliperidonepalmitate.

54. A device according to any one of claims 1 to 50, wherein one of thepharmaceutical components comprise an active pharmaceutical substancewhich is C₃₉ H₅₇ F N₄ O₄.

55. The device of any one of claims 52 to 54, wherein the activepharmaceutical substance and/or device is for use in the treatmentschizophrenia.

56. The device any one of claims 52 to 55, wherein at least one other ofthe pharmaceutical components comprises a fluid in which the activepharmaceutical substance is suspended.

57. A substance for use as one of the pharmaceutical components in thedevice of any one of claims 1 to 50, comprising an active pharmaceuticalsubstance which is INVEGA TRINZA™ (see Appendix; section 11).

58. A substance for use as one of the pharmaceutical components in thedevice of any one of claims 1 to 50, comprising an active pharmaceuticalsubstance which comprises a racemic mixture of (+)- and (−)-paliperidonepalmitate.

59. A substance for use as one the pharmaceutical components in thedevice of any one of claims 1 to 50, comprising, an activepharmaceutical substance which is C₃₉ H₅₇ F N₄ O₄.

60. The substance of any one of claims 57 to 59 for use in the devicefor the treatment schizophrenia.

While the invention has been described in terms of particular variationsand illustrative figures, those of ordinary skill in the art willrecognize that the invention is not limited to the variations or figuresdescribed. In addition, where methods and steps described above indicatecertain events occurring in certain order, those of ordinary skill inthe art will recognize that the ordering of certain steps may bemodified and that such modifications are in accordance with thevariations of the invention. Additionally, certain of the steps may beperformed concurrently in a parallel process when possible, as well asperformed sequentially as described above. Therefore, to the extentthere are variations of the invention, which are within the spirit ofthe disclosure or equivalent to the inventions found in the claims, itis the intent that this patent will cover those variations as well.

The invention claimed is:
 1. A device for training or aiding users in aproper mixing of pharmaceutical components, the device comprising: ahousing; a microcontroller disposed in the housing; and a displayconfigured to alert a user to a status of the device as determined bythe microcontroller, wherein the microcontroller is configured toindicate via the display whether the motion and/or orientation of thehousing being shaken during one of a drug mixing and administration, ora training event meets one or more predetermined thresholds indicativeof satisfactory mixing of the pharmaceutical components for delivery,and wherein the microcontroller is configured to indicate via thedisplay a state of mixing or simulated mixing of the pharmaceuticalcomponents in a real-time manner.
 2. The device of claim 1, wherein thehousing extends along a longitudinal axis.
 3. The device of claim 2,wherein the housing comprises a major longitudinal axis.
 4. The deviceof claim 3, wherein the housing is adapted to receive a drug deliverydevice having a major longitudinal axis, and further adapted to alignthe major longitudinal axis of the device along the major longitudinalaxis of the drug delivery device.
 5. The device of claim 1, furthercomprising a motion/orientation detection device disposed in or on thehousing and electrically connected to the microcontroller so that themicrocontroller is configured to detect a motion and/or orientation ofthe housing.
 6. The device of claim 1, wherein the microcontroller isconfigured to detect whether the motion or orientation of the housingbeing shaken during one of a pharmaceutical administration or a trainingevent meets one or more predetermined thresholds including one or moreof: magnitude of the force applied during the shaking, the orientationof the housing, and duration of such shaking.
 7. The device of claim 1,wherein the microcontroller is configured to notify a user via thedisplay as to whether the motion or orientation of the housing beingshaken during one of a drug administration or a training event meets oneor more predetermined thresholds including one or more of: magnitude ofthe force applied during the shaking, the orientation of the housing,and duration of the shaking.
 8. The device of claim 1, furthercomprising a power source disposed in or on the housing.
 9. The deviceof claim 8, wherein the power source is connected to the microcontrollerto provide power to the microcontroller and/or the display.
 10. Thedevice of claim 1, wherein the display is mounted on an external surfaceof the housing for notifying a user as to the status of the device. 11.The device of claim 1, wherein the microcontroller is configured tochange progressively the color and/or pattern of one or more displayelements on the display as shaking takes place until sufficient shakinghas taken place for satisfactory mixing or satisfactory simulated mixingof the pharmaceutical components for delivery.
 12. The device of claim1, wherein the microcontroller is configured to display at least twotypes of display elements on the display which are grouped together inat least two discrete portions of the display prior to commencement ofshaking, and which progressively mix with each other on the display solong as shaking continues at a sufficient enough or pre-defined forceand/or for a sufficient enough or predefined duration, until themicroprocessor determines that sufficient shaking has taken place forsatisfactory mixing or satisfactory simulated mixing of thepharmaceutical components for delivery, at which time the at least twotypes of display elements are wholly integrated with each other in aregular pattern across the display.
 13. The device of claim 12, whereinthe pharmaceutical components to be mixed consist of a first componentand a second component, wherein the at least two types of displayelements consist of a first type of display element corresponding to thefirst component and a second type of display element corresponding tothe second component.
 14. The device of claim 1, further comprising astart switch electrically connected to the microcontroller.
 15. Thedevice of claim 14, wherein the start switch is configured to activatethe microcontroller from a power conservation mode into an active modeupon detection of movement of the housing during one of a drug mixingand administration event, or a training event.
 16. The device of claim15, further comprising a power source disposed in or on the housing,wherein the microcontroller is configured, during the power conservationmode, to draw reduced power with respect to the active mode, or no powerat all, from the power source.
 17. The device of claim 1, wherein themicrocontroller is configured to detect, during one of a drug mixing andadministration or a training event, when shaking of the housing hasended prematurely for sufficient enough mixing or sufficient enoughsimulated mixing of the components, or if the level of shaking vigor ofthe housing has reduced to a level below a pre-set threshold forsufficient enough or sufficient enough simulated mixing of thecomponents, and, if so, to enter a pause mode to restart shaking. 18.The device of claim 17, wherein the pause mode is notified to the uservia the display.
 19. The device of any one of the preceding claims whendependent on claim 8, wherein the microcontroller is configured todetect low remaining power availability of the power source.
 20. Thedevice of claim 1, wherein the microcontroller is configured to detectan error or fault in the functioning of the device.
 21. The device ofclaim 19, wherein, when the microcontroller detects a low remainingpower availability of the power source, it performs one or more of thefollowing: issues an alert representative of the low remaining poweravailability to the user; and/or prevents activation of thepharmaceutical delivery device for delivery of the pharmaceuticalcomponents to a user.
 22. The device of claim 1, further comprising adelivery device identification unit in communication with themicrocontroller.
 23. The device of claim 22, wherein the delivery deviceidentification unit is configured to read data stored on a deliverydevice contained in use in the housing, wherein the data stored on thedelivery device identifies is characteristic the pharmaceuticalcomponents contained in the device and/or the delivery device.
 24. Thedevice of claim 23, wherein the data stored on the delivery devicecomprises one or more of: expiration date of the pharmaceuticalcomponents, whereby the microcontroller is configured to alert a uservia the display if the current date as determined by the microcontrollerexceeds the expiration date; and/or data identifying the pharmaceuticalcomponents contained within the delivery device, whereby themicrocontroller is configured to alert a user via the display if thedata identifying the pharmaceutical components does not match orsufficiently correspond to permitted pharmaceutical components as storedin the microcontroller or in memory connected thereto.
 25. The device ofclaim 24, wherein the data stored on the delivery device comprises oneor more of: expiration date of the pharmaceutical components, wherebythe microcontroller is configured to prevent activation of thepharmaceutical delivery device for delivery of the pharmaceuticalcomponents to a user if the current date as determined by themicrocontroller exceeds the expiration date; and/or data identifying thepharmaceutical components contained within the delivery device, wherebythe microcontroller is configured to prevent activation of thepharmaceutical delivery device for delivery of the pharmaceuticalcomponents to a user if the data identifying the pharmaceuticalcomponents does not match or sufficiently correspond to permittedpharmaceutical components as stored in the microcontroller or in memoryconnected thereto.
 26. The device of claim 5, wherein themotion/orientation device is an accelerometer.
 27. A method to direct auser on a proper drug mixing technique with the device of claim 1, themethod comprising at least the step of determining motion and/ororientation of the housing.
 28. The device of claim 1, wherein thepharmaceutical components comprise at least two phases.
 29. The deviceor method of claim 28, wherein at least one of the two phases is a solidphase and at least one of the two phases is a liquid phase.
 30. Thedevice or method of claim 28, wherein two of the at least two phases areliquid phases.